The olfactory organ, which gives rise to both the olfactory sensory neurons and a group of neuroendocrine cells containing gonadotropin- releasing hormone (GnRH), arises from the olfactory placode during development. GnRH is a hormone that has essential reproductive and neuromodulatory functions (Pfaff et. al., 1987) and Kallman's Syndrome in humans, characterized by anosmia and hypogonadism, has now been shown to result from the failure of the GnRH cells to migrate from the olfactory placode (Schwanzel-Fukuda et al., 1989; Legouis et al., 1991). While the development of the olfactory organ has been described after the time of olfactory placode differentiation, the early developmental events giving rise to the olfactory placode and its derivatives remain poorly understood. Two crucial unanswered questions in the field of olfactory biology will be addressed here: how does the olfactory placode differentiate and what is the lineage relationship between olfactory sensory neurons and GnRH cells? This proposal will address the question of which cellular and genetic processes control the initial development of the olfactory placode add subsequent differentiation of the GnRH cells and olfactory sensory neurons. Zebrafish will be used because of the ability to mark cells and follow them during development of live embryos. In addition, zebrafish provide a unique opportunity to screen for mutant phenotypes to identify genes important in the early development of the olfactory system and its derivatives.